Ependymoma gene expression profiles associated with histological subtype, proliferation, and patient survival
ACTA NEUROPATHOLOGICA
Authors: Lukashova-von Zangen, Inna; Kneitz, Susanne; Monoranu, Camelia-Maria; Rutkowski, Stefan; Hinkes, Bernward; Vince, Giles Hamilton; Huang, Bei; Roggendorf, Wolfgang
Abstract
Ependymomas are primary tumors of the central nervous system that typically originate from the walls of the cerebral ventricles or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based on histologic features and clinical parameters is difficult. The aim of this study was to investigate the molecular heterogeneity of ependymomas. We used cDNA microarrays and RT-PCR to examine gene expression in 47 ependymomas. We present results for five comparisons: (1) tumors from children and adults with poor versus favorable outcome, (2) tumors from children with poor versus favorable outcome, (3) tumors with high versus low proliferation indices, (4) subependymomas versus myxopapillary ependymomas, and (5) spinal versus intracranial ependymomas. For patients with an overall survival > 10 years after diagnosis, we identified 27 genes associated with favorable prognosis. In contrast, overexpression of BNIP3, MRC1, EPHB3, GLIS3, CDK4, COL4A2, EBP, NRCAM, and CCNA1 genes in tumors with high proliferation indices was associated with a poor outcome. Thirty genes, including ETV6, YWHAE, TOP2A, TLR2, IRAK1, TIA1, and UFD1L were found to be highly expressed in subependymomas but not myxopapillary ependymomas. Also, 30 genes were differentially expressed in spinal versus intracranial ependymomas. There was no relationship between expression profiles and tumor grade, patient age, and patient gender. Our results provide insight into specific molecular events underlying ependymoma tumorigenesis and may contribute to more accurate diagnosis and prediction of clinical outcome.
Identification of Vasculature-Specific Genes by Microarray Analysis of Etsrp/Etv2 Overexpressing Zebrafish Embryos
DEVELOPMENTAL DYNAMICS
Authors: Wong, Kuan Shen; Proulx, Kira; Rost, Megan S.; Sumanas, Saulius
Abstract
Signaling pathways controlling vasculogenesis, angiogenesis, and myelopoiesis are still poorly understood, in part because not all genes important for vasculature or myeloid cell formation have been characterized. To identify novel potential regulators of vasculature and myeloid cell formation we performed microarray analysis of zebrafish embryos that overexpress Ets1-related protein (Etsrp/Etv2/ER71), sufficient to induce vasculogenesis and myclopoiesis (Sumanas and Lin [2006] Development 121:3141-3150; Lee [2008] Cell Stem Cell 2:497-507; Sumanas et al. [2008] Blood 111:4500-4510). We performed sequence homology and expression analysis for up-regulated genes that were novel or previously unassociated with the zebrafish vasculature formation. Angiotensin H type 2 receptor (agtr2), src homology 2 domain containing E (she), mannose receptor C1 (mrc1), endothelial cell-specific adhesion molecule (esam), yes-related kinase (yrk/fyn), zinc finger protein, multitype 2b (zfpm2b/fog2b), and stabilin 2 (stab2) were specifically expressed in vascular endothelial cells during early development while keratin18 expression was localized to the myeloid cells. Identification of vasculature and myeloid-specific genes will be important for dissecting molecular mechanisms of vasculogenesis/angiogenesis and myelopoiesis. Developmental Dynamics 238:1836-1850, 2009. (C) 2009 Wiley-Liss, Inc.